Globally, FSWs who inject drugs (FSW-IDUs) are important `bridge' populations that can transmit HIV/STIs to the general population; however, interventions to reduce both their injection and sexual risks are lacking. The overall goal of this epidemiologic study is to simultaneously reduce high risk sexual and injection behaviors among FSW-IDUs in two Mexico-U.S. border cities, among whom HIV prevalence has recently increased from 2% to 14%; 46% had at least one active STI. Our specific aims are: Aim 1) To evaluate the efficacy of a behavioral intervention to decrease sharing of syringes and injection paraphernalia among FSW-IDUs. We hypothesize that FSW-IDUs in the active experimental injection risk reduction condition will report: (a) less receptive and distributive needle sharing; (b) less sharing of injection paraphernalia; (c) obtaining syringes and injection paraphernalia from safer sources. Aim 2) To evaluate efficacy of a behavioral intervention to increase condom use among FSW-IDUs in the context of ongoing drug use. We hypothesize that FSW-IDUs in the active experimental sexual risk reduction condition will: (a) report less unprotected vaginal and anal sex; (b) have fewer incident cases of specific STIs. Aim 3) To evaluate the joint effects of these two behavioral interventions to increase condom use and reduce sharing of needles/injection paraphernalia among FSW- IDUs. We hypothesize that the joint effect of these interventions will generate greater risk reductions compared to either intervention alone. Aim 4) To determine the extent to which theoretically-important components of our interventions (i.e., self-efficacy, outcome expectancies, attitudes, intentions) represent underlying mechanisms of change in primary outcomes (i.e., sexual and injection-related risk reductions). Aim 5) To explore subgroup differences in the efficacy of a) the sexual risk reduction intervention and b) the injection risk reduction intervention based on background characteristics, contextual factors, social factors and intrapersonal factors. To meet these aims, we will recruit 600 HIV-negative FSW-IDUs (300 each in Tijuana and Cd. Juarez) and randomize women to one of three time-equivalent groups (Group 1: injection risk intervention and didactic safer sex education; Group 2: sexual risk intervention and didactic safer injection education; Group 3: Both active injection and sexual interventions). In each city, cluster randomization will be used to minimize contamination. All women receive free STI treatment and will be followed-up at 4, 8 and 12 months. Our design allows us to `unpack' the intervention to determine whether its components are just as effective in reducing injection and/or sexual risks, or if the more intensive conditions are needed to alter the epidemiology of HIV/STIs, thus having direct, tangible policy implications for Mexico and the US. Interventions that reduce HIV risks among FSW-IDUs may curtail the burgeoning HIV epidemic in the U.S-Mexico border region, and have applicability to other resource-poor countries.Globally, FSWs who inject drugs (FSW-IDUs) are important `bridge' populations that can transmit HIV/STIs to the general population; however, interventions to reduce both their injection and sexual risks are lacking. The overall goal of this epidemiologic study is to simultaneously reduce high risk sexual and injection behaviors among FSW-IDUs in two Mexico-U.S. border cities, among whom HIV prevalence has recently increased dramatically. To our knowledge, this is the first study of its kind to be tested in any country, findings from which have particular relevance to resource-constrained environments. [unreadable] [unreadable] [unreadable]